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Objectives Topical resorcinol 15% is a self-treatment for painful hidradenitis suppurativa nodules and abscesses with good results in reducing pain and lesion duration. The aim of this study is to establish a 15% topical resorcinol formula, to develop a physicochemical and microbiological stability study and to further determine the compounding shelf-life in different package conditions following the European Pharmacopoeia (Ph. Eur.) specifications. Methods Physicochemical and microbiological stability studies of the formulation were conducted for 12 months at room temperature (25°C±2°C) in different package conditions: aluminium tubes (aluminium A7-99.7% varnish DF-6172), plastic tubes (low density polyethylene) and amber plastic containers (polyethylene terephthalate). High performance liquid chromatography (HPLC) was developed as a method of indicating the stability of the resorcinol formulation. A microbiological growth assay was also validated according to the Ph. Eur. Physical properties were inspected to determine parameters such as odour, colour, pH, emulsion phase and extensibility index and its evolution. Results The HPLC method was validated according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. At day 365, visual inspection remained unchanged only for preparations packaged in aluminium tubes. The pH did not vary by more than 0.3 units in all conditions. The extensibility index decreased in the preparations packaged in plastic and amber plastic containers. HPLC analysis conducted over 1 year did not show a degradation greater than 7% of resorcinol in the preparation in plastic and aluminium packages. The ability of ATCC strains to grow in resorcinol formulation was confirmed under the suitability test. Resorcinol packed in aluminium tubes achieved microbiological stability at day 365. Conclusions Only the formulation package in aluminium tubes showed physicochemical and microbiological stability of resorcinol for 12 months at room temperature (25°C±2°C).

[Introduction] Acquisition of reduced susceptibility to biocides may contribute to the dissemination of high-risk (HR) clones of carbapenemase-producing Klebsiella pneumoniae (CP-Kp). The aim of this study was (a) to determinate the activity of biocides against CP-Kp, and (b) to analyse the relationship between biocide activity and the presence of efflux pumps., [Methods] The minimal inhibitory concentrations (MICs) of 6 biocides (sodium hypochlorite, chlorhexidine digluconate, benzalkonium chloride, povidone-iodine, ethanol and triclosan) were determined in triplicate at 25 °C and 37 °C in Mueller-Hinton broth (MHB) and M9 minimum medium, against 17 CP-Kp isolates representing different clones (HR and no-HR), sequence-types (STs) and carbapenemases. Efflux pumps genes were detected by whole genome sequencing (MiSeq)., [Results] Median MICs were slightly higher at 37 °C than at 25 °C (p ≤ 0.05), except for benzalkonium chloride, triclosan and ethanol. MIC medians were much higher in MHB than in M9, except for triclosan. No significant differences were observed in the median MICs, regarding the type of clone, ST or carbapenemase; cepA, acrAB, kpnEF and oqxAB genes were detected in all isolates, whereas qacE and qacA were not detected; smvAR, and qacΔE genes were detected in 94% and 47% of isolates, respectively., [Conclusions] Triclosan, chlorhexidine digluconate, benzalkonium chloride and ethanol were the most active biocides. The activity of some biocides is affected by temperature and growth media, suggesting that standardised procedures for biocide susceptibility testing based on MIC determination are required. This activity, in terms of MICs, are not related to the type of clone, ST, carbapenemase or the presence of the efflux pump genes., [Introducción] La adquisición de sensibilidad reducida a los biocidas puede contribuir a la diseminación de clones de alto riesgo (HR) de Klebsiella pneumoniae productor de carbapenemasa (Kp-PC). El objetivo de este trabajo fue: (a) determinar la actividad de varios biocidas frente a Kp-PC, y (b) analizar la relación de dicha actividad con la presencia de genes codificantes de bombas de expulsión., [Métodos] Las concentraciones mínimas inhibitorias (CMI) de 6 biocidas (hipoclorito de sodio, digluconato de clorhexidina, cloruro de benzalconio, povidona yodada, etanol y triclosán) se determinaron por triplicado a 25 y 37 °C, tanto en caldo Mueller-Hinton (MHB) como en medio mínimo M9, frente a 17 aislados de Kp-PC representativos de diferentes clones (HR y no HR), secuenciotipos (ST) y carbapenemasas. Los genes de bombas de expulsión se detectaron mediante secuenciación masiva del genoma completo (MiSeq)., [Resultados] Las medianas de las CMI fueron ligeramente superiores a 37 °C que a 25 °C, excepto para cloruro de benzalconio, etanol y triclosán. Las medianas de las CMI fueron considerablemente superiores en MHB que en M9, excepto para triclosán; cepA, acrAB, kpnEF y oqxAB se detectaron en todos los aislados, mientras que qacE y qacA no se detectaron; smvAR y qacΔE se detectaron en el 94% y en el 47% de los aislados, respectivamente., [Conclusiones] La actividad de algunos biocidas se afecta por la temperatura y el medio de crecimiento. Esta actividad, en términos de CMI, no se relaciona con el tipo de clon, ST, carbapenemasa, ni con la presencia de genes que codifican bombas de expulsión., This study was funded by a grant (PI15-01172) from Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía Industria y Competitividad, the Spanish Network for Research in Infectious Diseases (RD16/0016/0001)-co-financed by European Development Regional Fund «A way to achieve Europe», Operative program Intelligent Growth 2014-2020.

This study analyzes the pharmacokinetic variability of piperacillin in non-critically ill patients with Enterobacteriaceae bloodstream infections (EBSI) and explores predicted clinical outcomes and piperacillin-related neurotoxicity under different renal conditions. Hospitalized, non-critically ill patients treated with piperacillin–tazobactam for EBSI were included. Four serum samples per patient were collected and analyzed. A population pharmacokinetic model was developed using the Pmetrics package for R. Monte Carlo simulations of various dosage regimens of 4 g piperacillin, administered q8 h or q12 h by short (0.5 h) or long (4 h) infusion, following the different glomerular filtration rate (GFR) categories used to classify chronic kidney disease (Kidney Disease: Improving Global Outcomes, KDIGO) to determine the probability of target attainment (PTA) using a free drug concentrations above the minimal inhibitory concentration (fT &gt, MIC) of 50% for efficacy and targets for piperacillin-associated neurotoxicity. Twenty-seven patients (102 samples) were included. Extended piperacillin infusions reached a PTA &gt, 90% (50%fT &gt, MIC) within the susceptibility range, although a loading dose did not greatly improve the expected outcome. Long infusions reduced the expected toxicity in patients with severe renal impairment. The study supports the use of extended infusions of piperacillin in non-critically ill patients with EBSI. No benefits of a loading dose were expected in our population. Finally, extended infusions may reduce the risk of toxicity in patients with severe renal impairment.

The emergence and spread of carbapenemase-producing gram-negative bacteria is a major public health concern. We used data collected from microbiology laboratories as part of the PIRASOA program during 2014–2018 to study the epidemiology of carbapenemase-producing bacteria in Andalusia, Spain. Our findings highlight the importance of ongoing surveillance and epidemiologic studies for these bacteria.

The Pharmaceutical Technology Working Group and Pediatric Pharmacy Working Group of the Spanish Society of Hospital Pharmacy (SEFH)., Pediatric patients present changing physiological features. Because of the lack of land suitable for commercial management, pediatric specialties very often need to prepare extemporaneous formulations to improve the dosage and administration of drugs for children. Oral liquid formulations are the most suitable for pediatric patients. Clonidine is widely used in the pediatric population for opioid withdrawal, hypertensive crisis, attention deficit disorders and hyperactivity syndrome, and as an analgesic in neuropathic cancer pain. The objective was to study the physicochemical and microbiological stability and determine the shelf life of an oral solution containing 20 µg/mL clonidine hydrochloride in different storage conditions (5 ± 3 °C, 25 ± 3 °C, and 40 ± 2 °C). Using raw material with excipients safe for all pediatric age groups, two oral liquid formulations of clonidine hydrochloride were designed (with and without preservatives). Solutions stored at 5 ± 3 °C (with and without preservatives) were physically and microbiologically stable for at least 90 days in closed containers and for 42 days after opening. Two oral solutions of clonidine hydrochloride 20 µg/mL were developed for pediatric use from raw materials that are readily available and easy to process, containing safe excipients that are stable over a long period of time., This work was supported by Spanish Society of Hospital Pharmacy.

Background More data are needed about the safety of antibiotic de-escalation in specific clinical situations as a strategy to reduce exposure to broad-spectrum antibiotics. The aims of this study were to investigate predictors of de-escalation and its impact on the outcome of patients with bloodstream infection due to Enterobacteriaceae (BSI-E). Methods A post hoc analysis was performed on a prospective, multicenter cohort of patients with BSI-E initially treated with ertapenem or antipseudomonal β-lactams. Logistic regression was used to analyze factors associated with early de-escalation (EDE) and Cox regression for the impact of EDE and late de-escalation (LDE) on 30-day all-cause mortality. A propensity score (PS) for EDE vs no de-escalation (NDE) was calculated. Failure at end of treatment and length of hospital stay were also analyzed. Results Overall, 516 patients were included. EDE was performed in 241 patients (46%), LDE in 95 (18%), and NDE in 180 (35%). Variables independently associated with a lower probability of EDE were multidrug-resistant isolates (odds ratio [OR], 0.50 [95% confidence interval {CI}, .30–.83]) and nosocomial infection empirically treated with imipenem or meropenem (OR, 0.35 [95% CI, .14–.87]). After controlling for confounders, EDE was not associated with increased risk of mortality; hazard ratios (HR) (95% CIs) were as follows: general model, 0.58 (.25–1.31); model with PS, 0.69 (.29–1.65); and PS-based matched pairs, 0.98 (.76–1.26). LDE was not associated with mortality. De-escalation was not associated with clinical failure or length of hospital stay. Conclusions De-escalation in patients with monomicrobial bacteremia due to Enterobacteriaceae was not associated with a detrimental impact on clinical outcome.

[Objective] Our objective was to evaluate the impact of low versus borderline MIC of piperacillin/tazobactam on the clinical outcomes of patients with bacteraemia caused by Enterobacteriaceae who were treated with that antimicrobial., [Patients and methods] A prospective observational multicentre cohort study was conducted in 13 Spanish university hospitals. Patients >17 years old with bacteraemia due to Enterobacteriaceae who received empirical piperacillin/tazobactam treatment for at least 48 h were included. Outcome variables were clinical response at day 21, clinical response at end of treatment with piperacillin/tazobactam and all-cause 30 day mortality. Univariate and multivariate logistic regression analyses were performed., [Results] Overall, 275 patients were included in the analysis; 248 (90.2%) in the low MIC group (≤4 mg/L) and 27 (9.8%) in the borderline MIC group (8–16 mg/L). The biliary tract was the most common source of infection (48.4%) and Escherichia coli was the most frequent pathogen (63.3%). Crude 30 day mortality rates were 10.5% and 11.1% for the low MIC group and the borderline MIC group, respectively (relative risk = 1.06, 95% CI = 0.34–3.27, P = 1). Multivariate analysis of failure at day 21 and at end of treatment with piperacillin/tazobactam and 30 day mortality showed no trend towards increased clinical failure or mortality with borderline MICs (OR = 0.96, 95% CI = 0.18–4.88, P = 0.96; OR = 0.47, 95% CI = 0.10–2.26, P = 0.35; OR = 1.48, 95% CI = 0.33–6.68, P = 0.6)., [Conclusions] We did not find that higher piperacillin/tazobactam MIC within the susceptible or intermediate susceptibility range had a significant influence on the outcome for patients with bacteraemia due to Enterobacteriaceae., The study was funded by the Instituto de Salud Carlos III, Ministry of Economy and Competitiveness, Spain (FIS; PI10/02021) co-financed by European Development Regional Fund ‘A way to achieve Europe’ ERDF, Spanish Network for Research in Infectious Diseases (REIPI RD12/0015). J. A. R. is funded, in part, by an Australian National Health and Medical Research Council Research Fellowship (APP1048652).